Mutations in PINK1 and Parkin are causal for Parkinson's disease. Establishment of the role of PINK1 and Parkin in the removal of damaged mitochondria by mitophagy has elaborated one of the clearest mechanisms of neurodegeneration in Parkinson's laying the foundations for development of drugs now in clinical trials. In this lecture, I will present recent work my lab has undertaken to identify regulators of PINK1 activation and mitophagy. I will briefly summaries recent work from a whole kinome siRNA screen in which we identified the integrated stress response kinase EIF2AK1 (also known as HRI) as a negative regulator of PINK1 signalling. I will present unpublished findings from both phosphorylation analysis and TurboID proximity labelling screen of endogenous PINK1 which reveal new insights into PINK1 activation and mechanisms governing mitophagy initiation.